UV radiation has been shown to be a cause for a wide spectrum of skin damage, from premature aging to skin cancer, the most prevalent of all cancers in the United States. Skin cancer is a malignant neoplasm of the epidermis/dermis, i.e., it has uncontrolled growth, invades nearby tissue, and if left untreated, may spread throughout the body, metastasizing and eventually killing the host. Basal cell and squamous cell carcinomas represent the majority of skin cancer cases. The leading cause of death due to skin cancer is from malignant melanoma. It is estimated that over the lifetime 20% of United States population will develop skin cancer.
Besides skin cancer, there are also benign skin tumors and pre-malignant skin tumors. A benign skin tumor will not transform into skin cancer. Examples of benign skin tumors include, but are not limited to, moles, seborrheic keratoses, acrochordons (also called skin tags), epidermoid or sebaceous cysts, and dermatofibroma. A pre-malignant skin tumor is a confined mass that does not invade surrounding tissue, and is thus not yet cancerous by definition. However, over time they can dedifferentiate and become malignant. One common form of pre-malignant cancer is carcinoma in situ, where the cells are neoplastic and continue to multiply, but do not leave their confined space.
Skin tumors can be treated by various therapies, such as surgical removal or destruction via excision, cryosurgery, electro-cautery, chemo-cautery, and radiation or topical cytotoxic agents. If the malignant skin tumors are detected early, treatment is usually effective. However, the treatment can still be invasive.
An alpha adrenergic agonist is a drug that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Complete selectivity between receptor agonism is rarely achieved, some agents have partial selectivity.
The α adrenoceptor agonists have been used therapeutically for a number of conditions including hypertension, congestive heart failure, angina pectoris, spasticity, glaucoma, diarrhea, and for the suppression of opiate withdrawal symptoms (J. P. Heible and R. R. Ruffolo Therapeutic Applications of Agents Interacting with α-Adrenoceptors, p. 180-206 in Progress in Basic and Clinical Pharmacology Vol. 8, P. Lomax and E. S. Vesell Ed., Karger, 1991).
It was reported that activation of alpha-adrenoceptors with alpha-adrenoceptor agonists (e.g., clonidine, oxymetazoline, dexmedetomidine, etc) was associated with enhanced proliferation of human tumor epithelial breast cell lines or mouse mammary tumor cell line. See, e.g., Vázquez et al., Cancer Chemother Pharmacol. 2006 July; 58(1):50-61. Epub 2005 Nov. 15; and Bruzzone et al., Br J Pharmacol. 2008 October; 155(4):494-504. Epub 2008 Jul. 7. It was also reported that the alpha2-adrenoceptor antagonist yohimbine inhibited the proliferation and induced apoptosis of pancreatic cancer cells, suggesting that yohimbine can be used as an anticancer drug for pancreatic cancer. Shen et al., World J. Gastroenterol. 2008 Apr. 21; 14(15):2358-63. It was further reported that stimulation of alpha 2-adrenergic receptor inhibited cholangiocarcinoma, a cancer of the bile ducts. Kanno et al., Hepatology, 2002, Volume 35, Issue 6 (p 1329-1340). The current literature, while not extensive, does indicate that that alpha-adrenergic receptors may play a role in tumorogenesis, and that stimulation or antagonism of the these receptors can lead to either increased growth or suppression of tumor tissue, depending on the underlying cellular sub-type.
There is a need of improved noninvasive methods and compositions that would effectively prevent skin tumor formation or reduces skin tumor development, particularly for skin tumors induced by UV radiation. The present invention relates to such improved methods and compositions.